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Michael Gallagher
Senior Research Fellow, Histopathology

Biography

After gaining a PhD (Molecular Genetics) from University College Dublin, Michael Gallagher travelled to Singapore to pursue a career in stem cell biology as a Post-Doctoral Research Fellow at the Genome Institute of Singapore. Michael returned to Ireland in 2005 to establish, develop, and lead Ireland's only pure Cancer Stemness Research Group. In TCD, Michael has established a substantial, high-level research group, which has attracted more than 10 million euros of National and International funding directly and collaboratively, and produced a collection of quality publications including book chapters, reviews and research articles. The majority of cancer deaths are due to development of treatment-resistance disease. It is known that treatment-resistance is associated with tumour-initiating Cancer Stem Cells (CSCs). However, CSC-targeting has not been efficiently translated to the clinic. This is likely due to the complex organisation of CSCs as Stem-Progenitor-Differentiated cell Hierarchies within the tumour. Addressing this, Michael developed a single-cell analysis, CSC Discovery Pipeline, which facilitates the identification and characterization of CSC hierarchies. To date, our research has identified novel CSCs in lung, prostate, and oesphageal cancers, as well as a CSC Hierarchy in ovarian cancer. In 2017, Michael became the first researcher to demonstrate the treatment-resistance is the property of specific types of CSC (CSCRES), and not a universal property as previously believed. This is likely to impact upon future approaches to clinical targeting of CSC. Michael's on-going 'CSCRES Target' research aims to identify specific, treatment-resistant CSC in multiple malignancies, and to develop approaches through which these can be targeted in the clinic.

Publications and Further Research Outputs

Peer-Reviewed Publications

Lynham-Lennon N, Heavey S, Sommerville G, Bibby B, Ffrench B, Quinn J, Gasch C, O'Leary JJ, Gallagher MF, Reynolds J and Maher S, microRNA-17 is downregulated in esophageal adenocarcinoma cancer stem cells and promotes a radioresistant phenotype, OncoTarget, 8, (7), 2017, p11400 - 11413 Journal Article, 2017 TARA - Full Text

Ffrench B, Gasch, Hokamp K, Spillane C, Blackshields G, Mahgoub TM, Bates M, Kehoe L, Mooney A, Doyle R, Doyle B, O'Donnell D, Gleeson N, Hennessy BT, Stordal B, O'Riain C, Lambkin H, O'Toole S, O'Leary JJ, and Gallagher MF., CD10-/ALDH- cells are the sole cisplatin-resistant component of a novel ovarian cancer stem cell network. Cell Death & Disease , Cell Death and Disease, 2017 Journal Article, 2017 TARA - Full Text

MacDonagh L, Gallagher MF, Ffrench B, Gasch C et al, Targeting aldehyde dehygrogenase 1 (ALDH1) to circumvent cisplatin resistance in NSCLC, OncoTarget, 2017 Journal Article, 2017 TARA - Full Text

Sulaiman, G, Cooke A, Ffrench B, Gasch C, Abdullai OA, O'Connor K, Elbaruni S, Blacksheilds G, Spillane C, Keegan H, McEneaney V, Knittel R, Rogers A, Jeffery IB, Doyle B, Bates M, d'Adhemar C, Lee M, Campbell EL, Moynagh P, Higgins DG, O'Toole S, O'Neill L, O'Leary JJ and Gallagher MF. , MyD88 is an essential component of retinoic acid induced differentiation in human pluripotent embryonal carcinoma cells. Cell Death & Differentiation (In Press)., Cell Death and Differentiation, 2017 Journal Article, 2017 Other

Claudia Gasch, Brendan Ffrench, John O'Leary and Michael F Gallagher, Catching Moving Targets: Cancer Stem Cell Targets, Therapy-Resistance & Considerations for Clinical Targeting, Molecular Cancer, 16, (1), 2017, p43- Journal Article, 2017 TARA - Full Text

Cancer stem cells: targeting the sub-populations with epigenetic agents. in, editor(s)Steven Gray , Epigenetic Cancer Therapy, Elsevier, 2015, [Brendan Ffrench, John O'Leary and Michael F Gallagher] Book Chapter, 2015

Gallagher MF, Salley V, Spillane C, Ffrench B, Martin C, Sheils O, Watson W and O'Leary JJ. , Regulation of Cell Cycle and Suppression of Osteoblast Differentiation Mechanisms by Prostate Cancer Stem-Like Holoclones, Journal of Clinical Pathology, 1, 2015, p11- Journal Article, 2015

McEvoy, L.M., O'Toole, S.A., Spillane, C.D., Martin, C.M., Gallagher, M.F., Stordal, B., Blackshields, G., Sheils, O., O'Leary, J.J., Identifying novel hypoxia-associated markers of chemoresistance in ovarian cancer, BMC Cancer, 15, (1), 2015, p547- Journal Article, 2015 DOI TARA - Full Text

Vencken SF, Sethupathy P, Blackshields G, Spillane C, Elbaruni S, Sheils O, Gallagher MF, O'Leary JJ, An integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell lines., BMC genomics, 15, 2014, p711 Journal Article, 2014 TARA - Full Text DOI

Ffrench B, Gasch C, O'Leary JJ, Gallagher MF, Developing ovarian cancer stem cell models: laying the pipeline from discovery to clinical intervention., Molecular cancer, 13, 2014, p262 Journal Article, 2014 TARA - Full Text DOI

d'Adhemar CJ, Spillane CD, Gallagher MF, Bates M, Costello KM, Barry-O'Crowley J, Haley K, Kernan N, Murphy C, Smyth PC, O'Byrne K, Pennington S, Cooke AA, Ffrench B, Martin CM, O'Donnell D, Hennessy B, Stordal B, Finn S, McCann A, Gleeson N, D'Arcy T, Flood B, O'Neill LA, Sheils O, O'Toole S, O'Leary JJ, The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer., PloS one, 9, (6), 2014, pe100816 Journal Article, 2014 DOI TARA - Full Text

Laios A, Mohamed BM, Kelly L, Flavin R, Finn S, McEvoy L, Gallagher M, Martin C, Sheils O, Ring M, Davies A, Lawson M, Gleeson N, D'Arcy T, d'Adhemar C, Norris L, Langhe R, Saadeh FA, O'Leary JJ, O'Toole SA, Pre-Treatment of Platinum Resistant Ovarian Cancer Cells with an MMP-9/MMP-2 Inhibitor Prior to Cisplatin Enhances Cytotoxicity as Determined by High Content Screening., International journal of molecular sciences, 14, (1), 2013, p2085-103 Journal Article, 2013 DOI TARA - Full Text

Furlong F, Fitzpatrick P, O'Toole S, Phelan S, McGrogan B, Maguire A, O'Grady A, Gallagher M, Prencipe M, McGoldrick A, McGettigan P, Brennan D, Sheils O, Martin C, W Kay E, O'Leary J, McCann A, Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer., The Journal of pathology, 226, (5), 2012, p746-55 Journal Article, 2012

Gallagher MF, Heffron CC, Laios A, O'Toole SA, Ffrench B, Smyth PC, Flavin RJ, Elbaruni SA, Spillane CD, Martin CM, Sheils OM, O'Leary JJ, Suppression of cancer stemness p21-regulating mRNA and microRNA signatures in recurrent ovarian cancer patient samples., Journal of ovarian research, 5, (1), 2012, p2 Journal Article, 2012

Karl Egan., Darragh Crowley., Paul Smyth, Sharon O'Toole, Cathy Spillane, Cara Martin, Michael Gallagher, Aoife Canney, Lucy Norris, Niamh Conlon, Lynda McEvoy2, Brendan Ffrench2, Britta Stordal, Helen Keegan, Stephen Finn, Victoria McEneaney, Alex Laios, Jens Ducre, Eimear Dunne, Leila Smith, Michael Berndt, Orla Sheils, Dermot Kenny, John O'Leary, Platelet Adhesion and Degranulation Induce Pro-Survival and Pro-Angiogenic Signalling in Ovarian Cancer Cells, PLoS ONE, 6, (10, e26125), 2011 Journal Article, 2011 TARA - Full Text

Gallagher MF, Flavin RJ, Elbaruni SA, McInerney JK, Smyth PC, Salley YM, Vencken SF, O'Toole SA, Laios A, Lee MY, Denning K, Li J, Aherne ST, Lao KQ, Martin CM, Sheils OM, O'Leary JJ., Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients., Journal of Ovarian Research, 2, (19), 2009 Journal Article, 2009 URL DOI TARA - Full Text

Gallagher MF, Flavin RJ, Elbaruni SA, McInerney JK, Smyth PC, Salley YM, Vencken SF, O'Toole SA, Laios A, Lee MY, Denning K, Li J, Aherne ST, Lao KQ, Martin CM, Sheils OM, O'Leary JJ, Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients., Journal of ovarian research, 2, 2009, p19 Journal Article, 2009 TARA - Full Text DOI

Heffron, C.C.B.B., Gallagher, M.F., Guenther, S., Sherlock, J., Henfrey, R., Martin, C., Sheils, O., O'Leary, J.J. , Global mRNA analysis to determine a transcriptome profile of cancer stemness in a mouse model , Anticancer Research, 27, (3A), 2007, p1319-1324 Journal Article, 2007 URL

Research Expertise

Description

1. Towards Clinical Targeting of Cancer Stem Cell Treatment-Resistance. It is widely believed that clinical targeting of tumour-initiating, treatment-resistant 'Cancer Stem Cells' (CSCs) can dramatically reduce mortality rates associated with malignancy. Before this can be achieved, the treatment-resistant properties of CSCs must be understood. In my early career I became the first cancer researcher to demonstrate that chemotherapy-resistance is the property of specific types of CSC within the tumour and not a universal CSC property as previously believed (Ffrench et al 2017, MacDonagh et al 2017). Having demonstrated this in two very different malignancies (ovary, [Ffrench et al 2017], and Lung [MacDonagh et al 2017]), it seems likely that similar observations will be reported in other malignancies. For the first time, these studies highlight that CSC therapy-resistance must be targeted by specific, rather than global, therapies. The importance of these findings is reflected in the recent acceptance of the study by the prestigious Nature journal 'Cell Death & Differentiation', and the inclusion of my article reviewing this (Gasch et al 2017) in the 'CSC Special Series' by the highly topical journal 'Molecular Cancer'. In the short time since its publication, the article has been accessed more than 650 times and included in the popular 'CSC News' website's newsletter (3000 subscribers). As an illustration of the importance of this work, this review highlights that the treatment-resistant component of the tumour expands during recurrence and, as such, requires a different approach to treatment. This radically changes our understanding of how CSC should be targeted. It is rewarding that my work, and TCD's support, will be recognised as this field develops in future and patients hopefully receive new, effective treatments. My on-going career aims to identify specific treatment-resistance CSCs in multiple malignancies, and to develop an approach through which these can be targeted in the clinic. 2. Controlling Differentiation of Human Pluripotency. While at TCD I have made an additional breakthrough through my characterisation of the role of key inflammation regulator 'MyD88' in the highly topical area of human pluripotency (Sulaiman et al 2017). This project, which allowed collaboration with Professor Luke O'Neil (School of Biochemistry, TCD) and one of the pioneers of Stem & Cancer Stem Cell research Professor Peter Andrews (University of Sheffield), demonstrated that key 'Differentiation Gatekeepers' such as MyD88 control the initial steps in the differentiation of at least some types of human pluripotent cells. As these pluripotent cells can differentiate to become any cell type within the body, the findings are of immense potential importance for regenerative medicine. In addition, as CSCs can no longer produce tumours when differentiated, this finding can hopefully be exploited as a novel cancer therapy. While this study is still In Press and as yet not yet widely reported, its importance is reflected in its acceptance by the prestigious Nature publication 'Cell Death and Differentiation'.

Recognition

Awards and Honours

Project Licence Holder, LAST Ireland (Animal Research) 2011-Present

Guest Lecturer (Stem & Cancer Stem Cell Biology), Maynooth University 2014


Last updated 21 September 2016 Paul Smyth (Email).